Liu Yunhua, Hu Xiaoxiao, Han Cecil, Wang Liana, Zhang Xinna, He Xiaoming, Lu Xiongbin
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
State Key Laboratory for Chemo/Bio Sensing and Chemometrics, College of Biology, Hunan University, Changsha, China.
Bioessays. 2015 Dec;37(12):1277-86. doi: 10.1002/bies.201500093. Epub 2015 Oct 7.
Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain-of-function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss-of-function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics.
细胞毒性化疗药物和特异性调节一种或多种参与癌症的蛋白质活性的靶向疗法。在过去几十年中，靶向癌症治疗取得了重大进展，这归因于对癌症发生和发展分子机制的日益深入了解。因此，已经开发出单克隆抗体和小分子来干扰特定的分子致癌靶点。一般来说，针对功能获得性突变的靶向治疗已取得成效。然而，使用标准药理学方法靶向肿瘤抑制基因的功能丧失性突变一直是一项重大挑战。目前正在开发包括合成致死和旁系脆弱性筛选在内的新方法，以靶向p53、PTEN和BRCA1/2中的基因缺陷。在此，我们回顾并总结了癌症基因组学、药物开发和分子癌症生物学方面的最新发现，这些发现有望在癌症治疗中靶向肿瘤抑制因子。
